To clarify the role of in vivo interferon activation in the recovery from acute hepatitis C and in the prediction of responses to interferon-alpha treatment in chronic hepatitis C, we measured concentrations of 2',5'-oligoadenylate synthetase in the serum of 14 patients with well-documented acute post-transfusion hepatitis C and 40 patients with histologically confirmed chronic hepatitis C. In the latter group, 16 received interferon-alpha treatment, while no specific treatment was given to patients with acute hepatitis C. Serum activity of 2',5'-oligoadenylate synthetase was measured in duplicate by radioimmunoassay. Four out of the 14 patients with acute hepatitis C recovered, and hepatitis in the remaining 10 became chronic. Serum 2',5'-oligoadenylate synthetase concentration in the acute stage of hepatitis was above 200 pmol/dL in all four patients who recovered and in only of two of the remaining 10 patients (p < 0.02, Fisher's exact test). The 16 chronic hepatitis C patients who received interferon-alpha treatment were classified into sustained responders, relapsed responders and nonresponders, as judged by their responses to the treatment. Among the three groups, there was no significant difference in the mean concentrations of 2',5'-oligoadenylate synthetase either before the treatment or in the peak concentrations during the treatment. We conclude that activation of in vivo interferon in the acute stage favors recovery from acute hepatitis C, and 2',5'-oligoadenylate synthetase concentration cannot predict the responses to interferon-alpha treatment in patients with chronic hepatitis C.